Effect of an Inhaled Glucocorticoid-long-acting Beta Adrenergic Agonist on Endothelial Function in COPD

NCT ID: NCT01209715

Last Updated: 2014-08-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2012-05-31

Brief Summary

In the present study, the investigators wish to address the effect of a glucocorticoid/long-acting beta-agonist preparation on endothelial function in COPD patients who do not currently smoke (ex-smokers) by measuring endothelium-dependent (albuterol response) and endothelium-independent (NTG response) vasodilation in the bronchial artery, reflecting endothelium-dependent and endothelium-independent vasodilation (drug-induced increase in Qaw, ΔQaw). With this approach the investigators will test the hypothesis that in stable ICS-naïve COPD patients, endothelium-dependent vasodilation is restored with a glucocorticoid/long-acting beta-agonist preparation, presumably resulting from the glucocorticoid component.

Detailed Description

To test the premise and to characterize the time dependence of the responses, the investigators propose the following two aims:

1. To determine the effect of a medium dose glucocorticoid/long-acting beta-agonist preparation (250 μg fluticasone plus 50 μg salmeterol) administered for 3 weeks on inhaled albuterol and sub-lingual NTG induced vasodilation in the bronchial artery, as assessed by ΔQaw in stable glucocorticoid-naïve COPD patients, and to re-assess the responses after a 3 week glucocorticoid/long-acting beta-agonist washout period.

2. To determine inhaled albuterol and sub-lingual NTG-induced vasodilation (ΔQaw) before, and 30 min and 120 min after a single medium dose of an ICS (220 μg fluticasone) in stable glucocorticoid- naïve COPD patients.

For both aims, the protocol design will be placebo-controlled and double-blind. For the second aim, only fluticasone pretreatment will be possible because the salmeterol component of the fluticasone/salmeterol combination preparation could influence albuterol responsiveness irrespective of any glucocorticoid effect. The timing of the endothelial function measurements in the long-term glucocorticoid/long-acting beta-agonist protocol and single dose ICS protocol is based on the past experience with ICS on airway vascular function. Single dose effects were seen within 15-30 min and waned by 90 min (25,26), while long-term treatment effects were no longer seen 3 weeks after ICS withdrawal (16).

Conditions

COPD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: DOUBLE

Study Groups

Matching Placebo

Participants will be treated with placebo twice a day for 3 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

participants will be assigned to 3-weeks treatment of inhaled placebo twice a day

Fluticasone /salmeterol

Intervention Type: DRUG

Participant will be assigned to a 3-weeks treatment with inhaled fluticasone/salmeterol or matching placebo

Fluticasone/salmeterol

Participants will be assigned to inhaled fluticasone/salmeterol twice a day for 3 weeks.

Group Type: ACTIVE_COMPARATOR

Fluticasone /salmeterol

Intervention Type: DRUG

Participant will be assigned to a 3-weeks treatment with inhaled fluticasone/salmeterol or matching placebo

Interventions

Placebo

participants will be assigned to 3-weeks treatment of inhaled placebo twice a day

Intervention Type: DRUG

Fluticasone /salmeterol

Participant will be assigned to a 3-weeks treatment with inhaled fluticasone/salmeterol or matching placebo

Intervention Type: DRUG

Other Intervention Names

Advair 250/50

Eligibility Criteria

Inclusion Criteria

• Smoking history of at least 10 pack-years and to have quit smoking at least 1 year before the study. -Diagnosis of COPD
• Post-bronchodilator FEV1 of less than 75% of predicted and FEV1/FVC ratio less than 0.7 (GOLD stage ≥2).
• At entry into the study, the subjects will have to be clinically stable; they will be allowed to use short-acting and long-acting β2 - adrenergic agonists and cholinergic antagonists as their usual airway medication.

Exclusion Criteria

• Women of childbearing potential who do not use accepted birth control measures; pregnant and breast feeding women.
• Use of cardiovascular medications that cannot be held on the study days
• Use of oral airway medications or anti-inflammatory agents
• Subjects with known beta-adrenergic agonist or NTG intolerance
• Acute respiratory infection within four weeks prior to the study
• A body mass index > 30

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Adam Wanner

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adam Wanner, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami School of Medicine

Miami, Florida, United States

Countries

United States

Other Identifiers

114279

Identifier Type: -

Identifier Source: org_study_id